The objectives of this subproject are (1) to study the distribution, metabolism, excretion, persistence, and drug interactions of long-acting exogenous opioids (narcotics) using methadone and LAAM as prototypic agents in methadone maintained patients; (2) to extend studies of the physiological effects of methadone and LAAM, as well as the effects of other pharmacotherapeutic agents in chemical dependency, and drug free treatment in chronic maintenance patients during treatment and following detoxification from methadone; and (3) to determine the natural history of diseases common in addicts during treatment.